HISTOLOGY FULL-TEXT

William A Beresford MA, D Phil ©
Professor of Anatomy
Anatomy Department, West Virginia University, Morgantown, USA

Chapter 21 SKIN

Skin/integument covers the body and serves many functions. It consists of a thick, protective, cornified, stratified squamous epithelium (epidermis), on a firm, dense CT lamina propria (dermis), and has special appendages, hair and nails, and accessory glands, sweat, sebaceous, and mammary glands (Chapter 29.D). Powerpoint

A EPIDERMIS (epithelium)

l Layers
l Stratum corneum of keratinized cells (outermost).
2 Stratum lucidum, a thin pale layer of keratin seen when the stratum corneum is very thick.
3 Stratum granulosum of cells with basophilic granules.
4 Stratum spinosum of keratinocytes/prickle epithelial cells.
5 Stratum germinativum, bordering on the BL.

2 Cytological details of the layers
l Stratum germinativum/basale

(a) Keratinocyte precursor cells, cuboidal or columnar in form, lie on a BL.
(b) Cells project down many small basal processes.
(c) The whole underside of the epithelium is indented by CT dermal papillae for effective attachment, nutrition, and sensation.
(d) Cells proliferate to replace lost surface cells.

2 Stratum spinosum

(a) Keratinocytes/prickle cells
... (i) Principal cell kind; ectodermal in origin; move upwards in the layer and continue to proliferate, despite the many desmosomes holding them together (which, with processing shrinkage, lead to the cells' spiny, prickly appearance).
... (ii) Cytoplasm is rich in keratin filaments, bundled into tonofilaments and increasing in number towards the keratin layer, and formed from prekeratin monomers.
(b) Melanocytes
... (i) Ectodermal; but migrated neural crest cells.
... (ii) Constitute l in 4 to l in l0 of basal epithelial cells.
... (iii) Deficient in tonofilaments and desmosomes.
... (iv) Synthesize melanin and transfer it via their long dendritic processes to neighbouring keratinocytes.
... (v) EM shows that the Golgi apparatus participates in forming the melanosome granules.
... (vi) Melanin is formed from tyrosine by the enzyme tyrosinase. Cells with melanin-forming ability can be revealed in a section by treating it with dihydroxphenylalanine (DOPA), which is oxidized to melanin.
... (vii) Albinos have an inborn error of metabolism, making them unable to synthesize melanin in the skin and eye.
... (viii) UV light causes greater melanin formation and a thickening of the keratin layer. Pituitary and adrenal hormones also increase pigmentation, which is a useful sign for diagnosis.
(c) Langerhans cells are poorly phagocytic, marrow-derived, specialized macrophages, with long dendrites. They are antigen-presenting cells, accessory to T-cell immunity.
(d) Merkel cells are sensory cells with vesicles and a polylobulated nucleus. They attach to disc-shaped endings of some of the axons that penetrate the epithelium.

3 Strata granulosum and corneum.
(a) Stratum granulosum cells form a kerato-hyaline matrix from their basophil granules, binding together packed tonofilaments within the cells to convert the cells to soft keratin. Other organelles and the nucleus vanish, while the plasmalemma thickens and toughens, to build a cornified envelope.
(b) Flattened, dead, keratinized, surface cells desquamate.
(c) Only with EM is keratin seen to be cellular. In the usual HE preparation it is eosinophilic, and often splits and breaks.
(d) Epidermis is thrown up into ridges - cristae cutis - on the palmar and plantar surfaces of the hands and feet: the basis of finger and palm prints.
(e) At the top of the ridges, spiralling holes open through the keratin to let out the sweat.
(f) Keratin layer may be very thick, for instance on the soles and palms. Such thick skin is hairless, and lacks sebaceous glands.
(g) The molecular epidermis:- Filaggrin is the protein of keratohyaline granules, and aggregates 'keratinocyte' keratins Nos. 5/14. These acidic-basic combinations of keratins (numbered indirectly according to Mr) are characteristic for particular classes of epithelia, e.g., simple versus squamous, and help in interpreting pathological changes. Directly under the plasmalemma is a complex of proteins that are made dense and insoluble - to constitute the "envelope" - by transglutaminase-mediated cross-linking. One protein of the cornified cell envelope is involucrin. Ceramide and other extracellular lipids surround the envelope to boost the barrier function.

B DERMIS (Corium)

l Divided into layers: papillary, fine-textured CT adjacent to the epidermis, and a deeper reticular layer.
2 Reticular layer is thick collagenous CT of a variable thickness, not always related to that of the overlying epidermis.
3 Elastic fibres of the dermis give skin its elasticity, but cause wounds to gape. Ruptured dermis often heals as a white line visible through the epidermis, e.g., a mother's stretch marks.
4 Has the usual cells of CT - fibroblasts, macrophages and other defensive cells, and sometimes pigment-bearing chromatophores/dermal melanocytes.
5 Smooth muscle of arrectores pilorum, nipples and scrotal dartos, and skeletal muscle in the scalp and face, are attached in the dermis.
6 Blood vessels are derived from arterial plexuses: a deep cutaneous plexus/rete, and a subpapillary plexus sending capillary loops up into dermal papillae. Lymphatics accompany blood vessels. Blood flow is varied greatly by shunts through glomi (coiled arteriovenous anastomoses), and by the constriction or relaxation of arterioles.
7 Nervous receptors (Chapter 12.B), with sensory nerve fibres are present; and autonomic nerve fibres:
.. vasomotor to vascular smooth muscle,
.. pilomotor to hair arrector muscles,
.. sudomotor to sweat glands.
8 Hair follicles and glands lie mostly in the dermis.

C SWEAT GLANDS (Glandulae sudoriparae)

l Single coiled tubules, lined by simple cuboidal light and dark cells; distributed over the body except for the lips, glans penis and inner prepuce.
2 Secretory part lies in the lower dermis, or subcutaneously in the hypodermis/superficial fascia. One tubule is cut through many times in one section.
3 The secretion, mainly water and electrolytes plus some lipids, is led to the epidermis through a duct, lined by stratified cuboidal epithelium, then through the living/Malpighian layer and a spiralling hole in the keratin. The gland's chloride channel is one that is impaired in cystic fibrosis.
4 Myoepithelial cells are seen within the basal lamina of the secretory tubule. Their contraction is under autonomic control.
5 The larger variety of gland seen in the axillary, perianal and perigenitalial regions is termed apocrine, in contrast to the eccrine glands in the majority. Apocrine glands become active with pubertal development of the ambosexual hair, and may be related to animals' scent glands.
6 The ceruminous glands of the external auditory meatus seem to be enlarged sweat glands, producing a secretion of pigmented lipids.

D SEBACEOUS GLANDS

l Pear-shaped, simple, branched alveolar, with large cells, usually looking vacuolated because their fatty content is dissolved out.
2 Several glands are clustered by the side of a hair follicle, into which they discharge the secretion - sebum. Their short duct is lined by stratified squamous epithelium.
3 Sebum, formed in a holocrine manner by the total breakdown of the cells, may lubricate the hair shaft, protect the skin from drying and moisture, and be bacteriostatic.
4 Lie independently of hairs on the labia minora, glans penis, in the oral mucosa by the red margin of the lips, and as the Meibomian glands of the eyelid. They are absent from the palms and soles.

E HAIR

l Varieties and sites
1 Lanugo - fine, fetal, hairy covering, shed at birth.
2 Replaced by the vellus - fine body hairs.
3 Scalp, eyebrow and eyelash hairs are thicker.
4 Ambosexual hair - pubic and axillary.
5 Masculine hair - face (beard), chest and extremities.

2 Hair development
l Hair is a hard keratin derivative of the epithelium of a hair follicle.
2 In development, an epithelial bud grows down from the young epidermis; a vascular CT dermal papilla invaginates the bud; in the bud a germinal matrix develops, forming the special keratin; and side buds form sebaceous glands.

3 Hair shaft comprises:

(a) Medulla, as the central core of soft keratin and sometimes air spaces. The medulla may be absent.
(b) Cortex of closely packed, elongated, hard-keratinized cells, formed without any intermediary kerato-hyaline granules developing. Melanin and other pigments may be incorporated in the cells during keratinization.
(c) Cuticle - outermost coat of shingled/imbricated cells, with their free edges projecting upwards.

4 Hair follicle

(a) Outer CT sheath and inner basal lamina (hyaline membrane).
(b) Vascular papilla lies directly under the synthesizing epithelial area, responsible for the upward growth of the hair and its inner root sheath.
(c) External root sheath is a continuation of the epidermal living layer, expanding to form the basal hair bulb.
(d) Internal root sheath forms a cuticle layer from which the other cuticle, on the hair, can separate at the level of entry of the sebaceous gland's duct. The internal root sheath thus comprises: (a) innermost cuticle cells, (b) Huxley's layer of cells with trichohyaline granules, (c) Henle's single, outer layer of clear cells.
(e) Epidermal germinal matrix, above the papilla, forms the hair's cuticle, cortex and medulla. NB - the appearance of cross-sections varies with the level in the hair follicle at which they are taken.
(f) Arrector pili of smooth muscle fastens the lower hair bulb's CT sheath to the upper dermis nearby.

5 Epithelial replacement and hair growth are cyclical, not constant activities. The hair stops growing, via a relatively short catagen period of regression or involution, to enter a long non-growing telogen phase of being a club hair, which eventually falls out. It is replaced during an anagen/growth phase by a new hair from the reactivated deep region of the follicle.

3 Pilomotor activity
Hairs are raised from their relaxed, inclined attitude by contraction of their arrectores pilorum muscles in response to cold, so that more insulating air is trapped near to the skin. Hairs also 'stand up' in fear and other emotional reactions.

F NAIL

l The horny plate of hard beta keratin is synthesized by
2 the proximal, germinal, part of the nail bed.
3 The nail bed comprises the living layers of the epidermis, ridged longitudinally, and lacking glands and follicles. Part of its germinal region is seen by the naked eye as the
4 lunule, the pale half-moon area just distal to the eponychium - an extension of the stratum corneum of the dorsal skin.

G SKIN FUNCTIONS

l Protection against water, bacteria, sunlight, mechanical forces, dehydration, cold, etc.
2 Retaining body fluids, i.e., protection against dehydration.
3 Temperature regulation by: (a) varying peripheral blood flow, (b) sweating, (c) hair elevation, and (d) insulation by adipose tissue under the skin. (Note that heavy sweating defeats 2 above.)
4 Food storage and fat metabolism in the subcutaneous hypodermis.
5 Vitamin D formation by the action of ultraviolet light.
6 Sensory appreciation of the environment by nervous receptors: Chapter l2.B.L.
7 Friction surface for motor tasks involving grasping, rubbing, scratching, etc.
8 Display and communication: social, sexual, and diagnostic. Many diseases distinctively affect the skin and its hair and nails.

Chapter 22 RESPIRATORY TRACT

The tract rhythmically expels spent air and takes in fresh through conditioning passages, conducting it to the respiratory portion of the lungs, where the walls of the air-filled chambers are thin enough to permit an exchange of gases between blood and air. The respiratory movements involve chemoreceptors, brain centres, the thoracic cage, and various muscles: these structures belong, together with the respiratory tract, in the respiratory system Powerpoint. The lungs also have important metabolic functions not directly related to gas exchange, e.g., the activation of circulating angiotensin I, and the inactivation of some other vasoactive agents.

A RESPIRATORY TRACT TO LUNGS

l Nasal cavity
l Divided by a hyaline-cartilage nasal septum in the midline.
2 Stratified squamous epithelium (hairy) of the nares changes to
3 a lining nasal mucosa of:
.. (a) pseudostratified, columnar, ciliated epithelium with mucus-secreting goblet cells, on
.. (b) a loose lamina propria, with many leucocytes, blood vessels, and mixed muco-serous glands.
4 Venous plexuses, to warm the air, underlie the epithelium.
5 Turbinate bones in the conchae support the mucosa.
6 A small part of the mucosa is olfactory, with a neuroepithelium (Chapter l2.B.5.la) and Bowman's glands.
7 Paranasal air sinuses open off the main cavity.
8 The folded pharyngeal tonsil, covered by pseudostratified, columnar, ciliated epithelium, lies posteriorly in the pharynx.

9 Nasal functions:

(a) air-filtering, material trapped in mucus is swept by the cilia towards the pharynx,
(b) air-warming,
(c) air-humidifying,
(d) olfaction,
(e) sensitivity for nasal reflexes such as sneezing,
(f) resonating the voice.

2 Larynx
l Hollow chamber, whose walls are supported by cartilages, connected by ligaments and membranes, and moved by skeletal muscles.
2 The extrinsic and intrinsic muscles move the larynx up and under the epiglottis in swallowing, and move the cartilages and tense the vocal cords during phonation and breathing.
3 The cartilages are hyaline tending to calcification, or elastic for the epiglottis, cuneiforms, corniculates, and the apices and vocal processes of the arytenoids.
4 Mucosa is mostly pseudostratified, columnar, ciliated epithelium with goblet cells, on a loose lamina propria rich in elastic fibres, mucous and mixed glands, leucocytes and sometimes lymphoid nodules.
5 Two constrictions occur: the false vocal cords/ventricular folds; and the lower, true, cords. The true vocal chords are elastic ligaments tensed by the adjacent vocalis muscle, and are covered with stratified squamous epithelium. There are no glands in their lamina propria.
6 The epiglottis, too, has stratified squamous epithelium on its exposed tip and upper surface.

3 Trachea
l Flexible, extensible tube, with an always-patent lumen.
2 Mucosa as for the larynx, and the cilia sweep towards the pharynx, but the elastic fibres run longitudinally as a layer between mucosa and submucosa.
3 Supporting C-shaped pieces of hyaline cartilage are incomplete on their oesophageal side.
4 The gap in the C is crossed by trachealis smooth muscle and CT.
5 Outer adventitia is fibro-elastic CT.

B LUNGS

The structure of the lungs reflects the way in which the air is moved:

(a) the lungs are covered by a slippery membrane and are enclosed in another membrane, adherent to the inner chest wall, with a potential space between;
(b) the lungs are stretched out against their considerable elasticity, so that this space remains only a potential one;
(c) the larger conducting tubes of the lung need firm cartilages in their walls to prevent their collapsing during the inspiratory sucking in of air.

l Bronchial tree serving the lungs
l Primary bronchi branch to form the
2 intrapulmonary lobar bronchi, branching to form segmental bronchi, then lobular bronchioles. After about 9-l2 generations of branching, bronchioles replace bronchi.
3 Terminal bronchioles lead to respiratory bronchioles, off which open the respiratory exchange units, and not just at the end, but along the bronchiole. [For efficiency, the branching, tubular architecture of air conductance overlaps slightly the honeycomb architecture of gas exchange.]
4 Bronchi resemble the trachea in structure, except that the cartilage pieces in the wall have very irregular shapes, and the smooth muscle forms a nearly complete layer - muscularis mucosae - between the cartilages and the lumen.
5 Bronchioles are smaller than bronchi:
.. they have no cartilages;
.. their elastic fibres merge with those of the surrounding lung tissue;
.. the epithelium changes to simple, low ciliated columnar with a few goblet cells;
.. no mucous glands are present in the lamina propria, where the smooth muscle is relatively substantial.
6 Sharing the connective tissue of the branching bronchi are blood vessels, nerves and lymphatic vessels, entering or leaving at the hilum or lung root.
7 Hilar structures include arteries (bronchial and pulmonary), veins, lymphatics (from two systems), bronchi, lymph nodes, ganglia, nerves (to bronchial, bronchiolar, and vascular smooth muscles; and sensory), and adipose and other CT.
The carotid body-like glomus pulmonale in the pulmonary artery's adventitia is of uncertain function.

2 Mucosa of the lower airway

Cell types in the epithelium:
- (a) ciliated columnar cells, with lysosomes and some microvilli;
- (b) mucus-secreting goblet cells;
- (c) basal 'undifferentiated' cells to replace the specialized kinds;
- (d) Clara's non-ciliated bronchiolar secretory cells with granules and GER;
- (e) neuroendocrine cells;
- (f) lymphocytes migrated from the lamina propria.
A sheet of sticky mucus is moved by ciliary action over the mucosa to catch and remove particles - the mucociliary escalator.
The basal lamina typically is thick.
Muco-serous mixed glands, where present in the lamina propria, are small, compound tubular, and respond under nervous control to irritant stimuli, e.g., smoke.

3 Respiratory chambers
l Respiratory bronchiole has simple, low columnar or cuboidal bronchiolar and ciliated cells; elastic fibres and smooth muscle support the epithelium's BL.
2 Opening out along the respiratory bronchiole are alveoli, whose openings are ringed by smooth muscle.
3 At the end of the respiratory bronchiole are one or more long alveolar ducts.
4 Alveolar ducts can be viewed as being three to six atria, vestibules, leading to alveolar sacs, made up of varying numbers of alveoli.
Processing distortions in lung slides often make the atria and sacs hard to make out.
5 One alveolus or cubicle shares an alveolar wall with the ones adjacent and backing on to it. The wall is thus interalveolar and carries the many capillaries, whose blood is to receive oxygen and give up carbon dioxide.
6 Angiotensin converting enzyme in pulmonary capillaries cleaves angiotensin I to make it the potent angiotensin II.

4 Interalveolar wall
l Air side - continuous alveolar epithelium with:
.. (a) type I pneumocytes/squamous cells; and
.. (b) pneumocytes type II/septal or great alveolar cells, with prominent lipid cytosomes/ multilamellar bodies in their cytoplasm.
2 Surfactant is a stabilizing fluid film of lipids (90%) and proteins (10%), covering the epithelium and lowering surface tension. The principal surface-active agent is the lipid, dipalmitoyl phosphatidylcholine (DPPC). The type II cells synthesize this film, but also are the stem cell to replace themselves and Type I cells. Cytosomes are stored surfactant.
3 Alveolar macrophages/dust cells lie free in the alveoli.
4 Alveolar epithelium lies on a basal lamina sometimes merging with, and sometimes separated from, the
5 basal lamina of a blood capillary, on which lies an
6 unfenestrated endothelium on the blood side.
7 Where the two basal laminae are separated, the space - zona diffusa - is taken by elastic and reticular fibres, fibroblasts, macrophages and other CT cells.
8 The pulmonary blood-air barrier can therefore be as thin as 300 nm, and has a very extensive area.
9 Communication between adjacent alveolar sacs is through holes in the wall - alveolar pores.
l0 Basal laminae, fibres, and surfactant maintain the shape and patency of alveoli during respiration.

5 Pleurae are fibro-elastic vascular membranes with mesothelial coverings. From the visceral pleura, CT septa run in to subdivide the lung into lobules and carry lymphatic and venous vessels.

C RESPIRATORY TRACT

l Development
l From an endodermal bulge on the foregut, which gives the trachea, then two buds for the bronchi and lungs.
2 Continued budding and branching, and enclosure of the hollow buds by mesenchyme, produce a system of cuboidal epithelium-lined tubules with surrounding differentiating CT and vessels.
3 Early development thus is analogous to that of a compound exocrine gland, until the later phase, when the pulmonary alveoli form. Inadequately developed alveoli, with no surfactant, are a major hazard of premature birth.
4 Surfactant comprises lipids, and surfactant glycoproteins SP-A, -B, -C, & -D, which variously cause the lamellar material to become a monolayer, enhance the lowering of surface tension, stabilise the lipids, and modify host defences.
5 For the development of glands and the lung, complex mesenchymal-epithelial inductive (instructional) interactions occur, and recur during repair and tumour development.

2 Respiratory protective mechanisms

Secretion of entrapping mucus by goblet cells and mixed glands,
which is swept pharynx-wards by the ciliary beating action.
Solitary lymphoid nodules and tonsils, and their lymphocyte progeny, for immune defence.
Phagocytic alveolar macrophages/dust cells.
Reflex coughing, sneezing, and constriction of bronchioles.
Secretion of serous bacteriolytic materials, e.g., defensins and lysozyme.
Upper airway recovers water and heat, preventing too much loss in the expired air.

Some protection is hazardous in that enzymes from WBCs can break down elastin; and activated lung macrophages stimulate fibroblasts to lay down movement-restricting collagen - an interstitial fibrosis.

Various defects in the arms and microtubules of cilia (primary ciliary dyskinesia) can prevent proper clearance and cause recurrent lung infection. Affected men are often infertile from an accompanying paralysis of sperm.

William A Beresford, Anatomy Department, School of Medicine, West Virginia University, Morgantown, WV 26506-9128, USA - - e-mail: -- wberesfo@wvu.edu -- wberesfo@hotmail.com -- beresfo@wvnvm.wvnet.edu -- fax: 304-293-8159